DESMOPRESSIN

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Desmopressin, also known as DDAVP (1-deamino-8-D-arginine vasopressin), is a synthetic analog of vasopressin, an antidiuretic hormone. 

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Desmopressin has multiple effects on the body, including increasing water reabsorption in the kidneys, decreasing urine output, and promoting platelet adhesion, which helps blood clotting. The main importance of desmopressin in the context of anesthesia and surgery includes:

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1. Hemostasis and coagulation: Desmopressin is used to treat bleeding disorders such as von Willebrand disease, mild hemophilia A, and platelet dysfunction. It can be administered to patients with these conditions undergoing surgery to reduce the risk of excessive bleeding.

2. Diabetes insipidus: Patients with central diabetes insipidus, a disorder characterized by excessive urination and extreme thirst due to a deficiency of antidiuretic hormone, may require desmopressin administration during the perioperative period to prevent dehydration and maintain electrolyte balance.

3. Urological procedures: Desmopressin can be used in patients undergoing urological procedures to reduce the risk of hemorrhage.

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Desmopressin has a longer half-life and greater selectivity for the vasopressin V2 receptors compared to vasopressin, which makes it a more potent and longer-lasting drug. Desmopressin's mechanism of action is mainly based on its interaction with V2 receptors in the kidneys and its effects on coagulation factors.

 

Here are the primary steps of desmopressin's mechanism of action:

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1. Binding to V2 receptors: Desmopressin binds to V2 receptors, which are mainly found in the renal collecting ducts. This binding triggers the activation of adenylate cyclase, an enzyme responsible for converting adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP).

2. Increased intracellular cAMP: The rise in intracellular cAMP levels in the renal collecting duct cells leads to the activation of protein kinase A (PKA).

3. Aquaporin-2 channel insertion: Activated PKA phosphorylates aquaporin-2 (AQP2) water channels, causing them to be inserted into the apical membrane of the renal collecting duct cells. This increases the permeability of the collecting ducts to water.

4. Enhanced water reabsorption: The increased water permeability in the collecting ducts promotes water reabsorption from the urine back into the bloodstream. This leads to decreased urine production and increased urine osmolality, ultimately resulting in antidiuresis and helping to maintain fluid balance in the body.

5. Hemostatic effects: Desmopressin also has effects on coagulation factors, particularly von Willebrand factor (vWF) and factor VIII. It stimulates the release of vWF and factor VIII from endothelial cells, which helps improve platelet adhesion and blood clotting in patients with bleeding disorders such as von Willebrand disease and mild hemophilia A.​

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                                                                                         Key points about Desmopressin

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• Desmopressin (DDAVP) is the V2 analog of arginine vasopressin.

 

• It stimulates the release of von Willebrand (vWF) from endothelial cells., leading to the enhancement of hemostasis.

 

• DDAVP shortens the bleeding time of patients with mild forms of hemophilia A or von Willebrand’s disease.

 

• DDAVP is administered slowly to avoid hypotension.

 

• Von Willebrand factor (vWF) is a large glycoprotein that mediates the adhesion of platelets to the subendothelium.

 

• It is known to have vasodilator properties.

 

• It can increase heart rate and decrease in systolic and diastolic blood pressure.

 

• DDAVP is also indicated as antidiuretic replacement therapy in the management of the central diabetes insipidus.

 

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